A Randomized Phase 2 Study to Evaluate the Safety and Efficacy of IP-001 as Adjuvant Therapy in Participants With Hepatocellular Carcinoma After Complete Radiological Response After Surgical Resection and Local Ablation or Local Ablation Alone
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 315
- 试验地点
- 1
- 主要终点
- Recurrence Free Survival
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of administration of intratumoral IP-001 injection at different dosages (volume and concentration) following local microwave ablation (MWA) or surgical resection and ablation in patients with hepatocellular carcinoma (HCC).
详细描述
This is a Phase 2, five-armed, randomized study designed to evaluate the safety and efficacy of administration of intratumoral IP-001 injection at different dosages (volume and concentration) following local ablation or surgical resection and local ablation in patients with hepatocellular carcinoma who have an intermediate or high risk of recurrence compared to curative ablation or ablation and surgical resection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at time of signing Informed Consent.
- •Has a diagnosis of hepatocellular carcinoma (HCC) documented radiologically by American Association for the Study of Liver Diseases (AASLD) criteria and/or histopathologically from a tumor biopsy.
- •Has a treatment plan to receive a curative ablation (MWA only) or a curative surgical resection and ablation, or where the patient may benefit from surgery and ablation or ablation prior to receiving anti-cancer therapy.
- •Has HCC with intermediate, high or very high risk of recurrence.
- •Has hepatic only HCC (disease confined to the liver only), defined by no extra-hepatic lesions greater than 1 cm in size.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patient with past or ongoing hepatitis C virus (HCV) infection will be eligible if the patient has completed HCV treatment at least 1 month prior to Day
- •Patient with controlled hepatitis B will be eligible if the patient meets the following criteria:
- •Antiviral therapy for hepatitis B virus (HBV) must be given for at least 4 weeks, and HBV viral load must be less than 500 IU/mL prior to treatment. Patients on active HBV therapy with viral loads under 500 IU/mL should stay on the same therapy throughout study treatment.
- •Patients who are hepatitis B core antibody (anti-HBc) positive, negative for HBsAg, and negative or positive for anti- HBs, and who have an HBV viral load under 500 IU/mL do not require HBV anti-viral prophylaxis.
- •Patients who are not exposed to unreasonable risks by continued use of the investigational agent in spite of progression of disease. Such criteria may include the following:
- •Absence of symptoms and signs indicating clinically significant progression of disease.
- •No decline in performance status, as measured by ECOG or Karnofsky or both.
- •Absence of symptomatic rapid disease progression requiring urgent medical intervention.
- •Ensure that patients are reconsenting to treatment with the Informed Consent clearly stating that retreatment is not standard of care.
- •Has adequate organ function as specified in the Adequate Organ Function Laboratory Values Table. Specimens must be collected within 14 days prior to Day
- •Hematological: Absolute neutrophil count ≥1500/µL or ANC of ≤1500/µL if there is a stable medical history of neutropenia per provider discretion; Platelets ≥40,000/µL; Hemoglobin ≥8.0 g/dL.
- •Renal: Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR GFR ≥30 mL/min for patients with creatinine levels >1.5 × institutional ULN
- •Hepatic: Total bilirubin ≤2 mg/dL OR direct bilirubin ≤ULN for patients with total bilirubin levels >2 mg/dL; AST (SGOT) and ALT (SGPT) ≤5 × ULN; Albumin (c) >2.6 g/dL
- •Coagulation: International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants
- •Retreatment Inclusion Criteria:
- •Patients receiving retreatment with IP-001 following intrahepatic recurrence must satisfy all of the following:
- •Radiographic recurrence remains amenable to curative-intent thermal ablation.
- •No symptomatic rapid disease progression requiring urgent systemic therapy or palliative intervention.
- •ECOG performance status remains 0-
- •No evidence of clinically significant hepatic decompensation.
- •No extrahepatic disease that would preclude additional local therapy.
- •The Investigator determines that additional thermal ablation remains clinically appropriate.
- •The patient continues to satisfy protocol safety requirements.
排除标准
- •Known allergic reaction to shellfish, crabs, crustacean, or any trial components used in trial treatment.
- •Has an active infection requiring systemic therapy.
- •Has a diagnosis of immunodeficiency or currently receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent), or any other form of immunosuppressive therapy within 7 days prior to treatment day (Day 1), or has plans to start treatment including >10 mg daily of prednisone equivalent or any immunotherapy.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents or immunosuppressive drugs). NOTE: replacement therapy (e.g., thyroxine or insulin) is not considered a form of systemic treatment and is allowed.
- •Has had an allogeneic tissue/solid organ transplant, or eligible for a liver transplant and/or on the liver transplantation waiting list.
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, active tuberculosis, or idiopathic pneumonitis.
- •Has received local therapy to the liver, ablation other than microwave ablation (i.e., alcohol ablation, transcatheter chemoembolization, transcatheter embolization, hepatic arterial infusion, local radiation/Stereotactic Body Radiation Therapy or radioembolization) less than 3 months prior to treatment.
- •Is receiving any of the following prohibited concomitant therapies less than 21 days from treatment or 5 drug elimination half-lives, whichever is shorter, prior to randomization:
- •Antineoplastic systemic chemotherapy or biological therapy.
- •Immunotherapy not specified in this protocol.
- •Systemic glucocorticoids for any purpose other than to modulate symptoms from an adverse event (AE) that is suspected to have an immunologic etiology. Inhaled or topical steroids are allowed, and systemic steroids at doses ≤10 mg/day prednisone or equivalent are allowed. Exception: steroids may be used for premedication prior to imaging.
- •Has received a live vaccine within 28 days prior to treatment Day
- •Retreatment Exclusion Criteria:
- •Development of symptomatic extrahepatic disease.
- •ECOG >2 attributable to cancer progression.
- •Rapid multifocal progression requiring systemic therapy.
- •Investigator determination that further local therapy is unlikely to provide meaningful clinical benefit.
- •Withdrawal of consent.
研究组 & 干预措施
Arm A: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive intratumoral injection of IP-001 (10 mg/mL, 4 mL [low volume]) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: 1.0% IP-001 for injection (Drug)
Arm A: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive intratumoral injection of IP-001 (10 mg/mL, 4 mL [low volume]) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Surgical Resection and Local Ablation (Procedure)
Arm A: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive intratumoral injection of IP-001 (10 mg/mL, 4 mL [low volume]) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Local Ablation Alone (Procedure)
Arm B: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive local microwave ablation or surgical resection and local microwave ablation alone
干预措施: Surgical Resection and Local Ablation (Procedure)
Arm B: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive local microwave ablation or surgical resection and local microwave ablation alone
干预措施: Local Ablation Alone (Procedure)
Arm C: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive intratumoral injection of IP-001 (10 mg/mL, up to 12 mL [high volume]) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: 1.0% IP-001 for injection (Drug)
Arm C: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive intratumoral injection of IP-001 (10 mg/mL, up to 12 mL [high volume]) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Surgical Resection and Local Ablation (Procedure)
Arm C: Participants with ≤3 hepatic tumors that can be treated in one ablation session
Participants will be randomized 1:1:1 to receive intratumoral injection of IP-001 (10 mg/mL, up to 12 mL [high volume]) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Local Ablation Alone (Procedure)
Arm D: Participants with >3 hepatic tumors that can be treated in more than one ablation session
Participants will be randomized 1:1 to receive intratumoral injection of IP-001 (10mg/mL [high concentration], up to 12 mL) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: 1.0% IP-001 for injection (Drug)
Arm D: Participants with >3 hepatic tumors that can be treated in more than one ablation session
Participants will be randomized 1:1 to receive intratumoral injection of IP-001 (10mg/mL [high concentration], up to 12 mL) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Surgical Resection and Local Ablation (Procedure)
Arm D: Participants with >3 hepatic tumors that can be treated in more than one ablation session
Participants will be randomized 1:1 to receive intratumoral injection of IP-001 (10mg/mL [high concentration], up to 12 mL) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Local Ablation Alone (Procedure)
Arm E: Participants with >3 hepatic tumors that can be treated in more than one ablation session
Participants will be randomized 1:1 to receive intratumoral injection of diluted IP-001 (1 mg/mL [low concentration], up to 12 mL) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: 1.0% IP-001 for injection (Drug)
Arm E: Participants with >3 hepatic tumors that can be treated in more than one ablation session
Participants will be randomized 1:1 to receive intratumoral injection of diluted IP-001 (1 mg/mL [low concentration], up to 12 mL) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Surgical Resection and Local Ablation (Procedure)
Arm E: Participants with >3 hepatic tumors that can be treated in more than one ablation session
Participants will be randomized 1:1 to receive intratumoral injection of diluted IP-001 (1 mg/mL [low concentration], up to 12 mL) immediately following local microwave ablation or surgical resection and local microwave ablation
干预措施: Local Ablation Alone (Procedure)
结局指标
主要结局
Recurrence Free Survival
时间窗: From Date of Randomization until date of documented progression, assessed up to 60 months
Radiological assessments (Triphasic CT or MRI) of the chest, abdomen and pelvis will occur every 12 weeks for the first 2 years, then every 24 weeks thereafter. Recurrence will be determined by the investigator's radiological review per RECIST v1.1
次要结局
- Cancer Free Survival(Months 12 and 24)
- Overall Survival(Months 12 and 24)
- Recurrence Free Survival Rate(Months 12 and 24)
- Time to Intrahepatic Tumor Recurrence(From Date of Randomization until date of documented progression, assessed up to 60 months)
- Overall Survival Rate(Months 12 and 24)
- Time to Extrahepatic Tumor Recurrence(From Date of Randomization until date of documented progression, assessed up to 60 months)
研究者
Robert C. Martin
Director of the Division of Surgical Oncology Robert C. Martin
University of Louisville